PROJECT SUMMARY The proposed conference, titled ?Evolutionary Dynamics in Carcinogenesis and Response to Therapy,? will be held March 12-15, 2020 in Denver, Colorado. Two of the most critical issues in current cancer research are 1) defining the biological basis for the vast intratumoral heterogeneity observed in patients and 2) understanding the underlying processes in therapy resistance. Both issues stem from Darwinian evolutionary dynamics wherein selection forces are imposed on a population with heritable variability. In the instance of cancers, the interactions of individual cancer cells with one another, the surrounding tissues, and the immune system govern the evolution of cancers from carcinogenesis through treatment response (1-2). The concept of cancer as an evolutionarily guided process has been recognized for over forty years (14) but has focused mainly on the genetic diversity of cancers. The aim for this conference is to move away from the simplistic view of cancer evolution as a merely genetic phenomenon and to discuss instead how microenvironmental, immune cell, genetic, and epigenetic heterogeneity interact and how this influences cancer progression and therapy success or failure. Moreover, this conference will meet the need for practical application of evolutionary theory by providing a venue to synthesize concepts in evolutionary dynamics from basic cancer research into clinical applications. There is currently a dearth of opportunities in the United States for investigators to meet and share research on this subject. The program has been carefully designed to feature thought-provoking sessions on clonal evolution, generation of genomic and epigenomic diversity, mechanisms of dynamics and resistance, longitudinal dissection of resistance evolution, and evolutionary guided therapy. Attendance will help better disseminate the rapidly growing collection of research innovations. Collaboration and networking will also be encouraged by incorporating multiple opportunities for thoughtful discussion and meaningful interaction between participants.